Medicament dispenser

ABSTRACT

There is provided a medicament dispenser for use with a medicament carrier having a plurality of pockets ( 124 ) for containing medicament wherein said pockets are spaced along the length of and defined between two peelable sheets ( 112, 114 ) secured to each other, said dispenser having an internal mechanism for accessing said medicament contained within said medicament carrier. The internal mechanism includes indexing means comprising an index ratchet ( 120 ) which is moveable between a locked position whereby said ratchet engages a pocket on the medicament carrier and prevents further peeling thereof, and a release position allowing free movement of said medicament carrier. Actuation of the medicament dispenser actuates lid-driving means ( 134 ) to release the index ratchet from the medicament carrier to allow peeling thereof.

TECHNICAL FIELD

The present invention relates to a medicament dispenser for dispensingmedicament. The invention particularly relates to a device for use indispensing medicament in powder or tablet form.

BACKGROUND TO THE INVENTION

The use of inhalation devices in the administration of medicaments, forexample in bronchodilation therapy is well known. Such devices generallycomprise a body or housing within which a medicament carrier is located.Known inhalation devices include those in which the medicament carrieris a blister strip containing a number of discrete doses of powderedmedicament. Such devices usually contain a mechanism for accessing thesedoses, usually comprising either piercing means or means to peel a lidsheet away from a base sheet. The powdered medicament can then beaccessed and inhaled. Such a mechanism may also be used for dispensingmedicament in tablet form wherein peeling away the lid sheet from thebase sheet reveals a tablet for removal and subsequent consumption.

It is an object of the present invention to simplify the internalmechanism of a medicament dispenser for dispensing medicament in powderor solid form from a medicament carrier as described supra.

Yet another object of the present invention is to provide a device thatis refillable by insertion of a replacement cassette containing amedicament carrier. The cassette may be replaced when the medicamentcarrier is empty. The device is therefore more ‘environmentallyfriendly’ as the majority of the device may be retained and is notdisposable. It also allows the device to be fitted with additionalfeatures such as electronics which may not be cost effective on acompletely disposable device.

It is a further object of the present invention that the cassette may beeasily removed and that a new replacement cassette can be easilyinserted. It is also desirable that the operation of the medicamentdispenser be straightforward and non-complex and in particular that thenumber of separate steps involved in preparing the device for use beminimised. This is especially relevant where the device is designed foruse in the delivery of medicament in emergency or rescue situations(e.g. asthma attacks) where simplicity and ease of use is paramount.

When not in use it is desirable from a hygiene standpoint that amouthpiece, or other medicament exit channel, is provided with some kindof protective cover. The cover desirably acts both to prevent build-upof dirt and to prevent ingress of dirt into the body of the devicethrough the mouthpiece or channel, which might then be subject toinhalation or consumption by a patient. It is also desirable that thecover is in some way attached or mounted to the device to minimise therisk that the cover is misplaced or lost. It is therefore a furtherobject of the present invention for the body of the device to act as amouthpiece or exit channel cover when the device is in storage and thatthe cassette is movable relative to the body to enable the mouthpiece orchannel to be uncovered for use by the patient.

It is a further object of the invention to provide a medicamentdispenser device suitable for use with a large number of discrete dosesbut which is of an acceptable size for use by patients.

SUMMARY OF THE INVENTION

Accordingly, in one aspect the invention provides a medicament dispenserfor use with a medicament carrier having a plurality of pockets forcontaining medicament wherein said pockets are spaced along the lengthof and defined between two peelable sheets secured to each other, saiddispenser having an internal mechanism for accessing said medicamentcontained within said medicament carrier, said mechanism comprising,

-   a) an opening station for receiving a pocket of said medicament    carrier;-   b) peeling means positioned to engage a base sheet and a lid sheet    of a pocket which has been received in said opening station for    peeling apart such a base sheet and lid sheet, to open such a    pocket, said peeling means including lid driving means for pulling    apart a lid sheet and a base sheet of a pocket that has been    received at said opening station;-   c) an outlet, positioned to be in communication with an opened    pocket through which a user can remove medicament from such an    opened pocket; and-   d) indexing means for indexing in communication with said outlet,    pockets of a medicament carrier in use with said medicament    dispenser,    wherein said indexing means comprises an index ratchet which is    movable between a locked position in which said ratchet engages said    medicament carrier to prevent movement thereof and a release    position in which the ratchet disengages from the medicament carrier    to allow movement thereof for peeling open of a blister pocket.

In use, actuation of said medicament dispenser actuates said lid drivingmeans and reversibly disengages said index ratchet from said medicamentcarrier to allow peeling thereof (e.g. by enabling free movement of themedicament carrier). Suitably, the actuation of the lid driving meansand release of the index ratchet are coupled.

In the present invention, the lid driving means acts such as to draw themedicament carrier through the internal accessing mechanism, and inparticular to draw the carrier through the opening station for peelableopening thereof. In use, it is generally desirable that a single pocket(or other pre-determined number of pockets) is opened and that furtheropening is prevented. Herein, the index ratchet provides the means forachieving this desired function.

In use, the index ratchet is initially positioned (‘locked position’)such as to prevent travel of the medicament carrier. In response toactuation of the dispenser however, the lid driving means is actuatedand the index ratchet reversibly released (‘release position’) to enablea defined degree of travel of the medicament carrier to the openingstation. The defined degree of travel corresponds generally to thatrequired to move one blister pocket to the opening station and open thepocket for release of a dose (generally, one pocket's worth) ofmedicament. Once the defined degree of travel has been undertaken, theindex ratchet again locks (‘locked position’) and thereby acts such asto prevent further movement of the medicament carrier and hence furtherpeeling thereof, until after the released dose of medicament has beendispensed to the patient.

The index ratchet may have any suitable form. In aspects, it comprises aratchet arm that is suitably, pivotally mounted on the dispenser. Theratchet arm is generally shaped (e.g. with a dog-leg end) to engageblister pockets of the medicament carrier and located within themedicament dispenser to ensure that such engagement occurs in ratchetfashion.

Suitably, in the locked position the index ratchet engages a pocket onsaid medicament carrier and in the release position said pocket isdisengaged. When the pocket is engaged the medicament carrier isprevented from moving within the dispenser, but when dis-engaged themedicament carrier is movable within the dispenser for peelable openingof a pocket thereof.

Suitably, the index ratchet is positioned to cam in and out ofengagement with a blister pocket of the medicament carrier. In aspects,the index ratchet cams in and out to locate directly behind the blisterpocket of a medicament carrier, thereby providing consistent (single)pocket feed to the opening station.

Suitably, the medicament dispenser further comprises an indexing leverfor actuating said dispenser (i.e to actuate the lid driving means andrelease the index ratchet from said medicament carrier to allow peelingthereof).

Typically, said indexing lever comprises moving means (e.g. cam-form)for moving said index ratchet between locked and release positions, suchthat actuation of said lever from a rest position releases saidmedicament carrier for peeling thereof.

Typically, said indexing lever also comprises engagement means (e.g. alever ratchet) for engaging said lid driving means.

Suitably, said lid driving means comprises an index gear and a drivegear which are interconnected so that the rotation of one correlateswith the rotation of the other.

Suitably, said lid driving means comprises a wheel on which the lidsheet is wound up.

Typically, said lid sheet wheel has an effective winding surface, thediameter of which increases after every use of the dispenser as the lidsheet winds around the wheel.

In order to ensure that the same dose is dispensed every time, that is,only one medicament pocket is opened for every actuation of thedispenser, the dispenser may further comprise a lever stop means tolimit the extent of movement of said index lever and thereby said liddriving means, in order to control the length of medicament carrierpeeled by said peeling means. Hence, the medicament carrier is indexedby the same amount each time and a uniform, consistent dose is alwaysdispensed.

In one aspect, the dispenser further comprises compensating meanspositioned between said opening station and said lid sheet wheel forreducing the length of said lid sheet therebetween to compensate for anyincrease in the diameter of the effective winding surface of the liddriving means during use of the dispenser.

Typically, the compensating means takes the form of a flexible member.The flexible member may take the form of a flexible elongate arm aboutwhich the lid sheet is fed. The arm may flex inwards as tension in thelid sheet increases, and thus shorten the length of lid sheet betweenthe opening station and the lid driving means.

Suitably, the compensating means takes the form of a spring whichreduces in length as tension increase in the lid sheet between theopening station and the lid driving means. Typically a piston head ismounted on one end of the spring about which the lid sheet is fed. Theother end of the spring may be fixed. As tension in the lid sheetincreases the piston is driven down onto the spring.

Suitably, the compensating means takes the form of a sprung-loadedtensioner.

Suitably, the flexible member is resilient so that on removal of tensionfrom the lid sheet, the flexible member will return to its restposition. Thus, the internal mechanism can be reloaded with a newmedicament carrier after the used carrier is removed.

In another aspect, the dispenser comprises a clutch means to adjust forany increase in the diameter of the effective winding surface of the liddriving means during use of the dispenser. In one aspect, the clutchmeans communicates with the indexing means and the lid driving means,and comprises a gearing surface defining plural gear engagementpositions; and plural gear teeth for engaging said plural gearengagement positions, wherein the plural gear teeth are arranged suchthat at any one time only a single gear tooth engages a single gearengagement position.

It will be appreciated that, in use, the clutch means acts to compensatefor the increase in diameter of said effective winding surface of thelid driving means. The clutch means allows for slippage when the tensionin the lid sheet is greater than the force required to peel apart thelid sheet and the base sheet.

It will be appreciated that in total, the clutch means effectivelydefines a number of individual gear positions which is greater than thenumber of gear engagement positions. This is therefore advantageous overa traditional slipping clutch arrangement comprising intermeshing gearwheels, where the effective number of individual gear positions definedis either equal to, or no more than, the number of gear engagementpositions defined by one of the gear wheels. The clutch means herein isalso typically more compact than traditional slipping clutcharrangements e.g. because it enables smaller gearing surfaces to beemployed.

Suitably, the gearing surface and plural gear teeth are arranged suchthat the number of individual gear positions defined is equal to thenumber of gear engagement positions multiplied by the number of gearteeth. In one example, if the gearing surface defines 60 gear engagementpositions and there are 6 gear teeth, then up to 360 individual gearpositions are definable (e.g. 10 resolution on a rotating gear system).

Suitably, the gearing surface defines from 20 to 100, preferably from 40to 80 gear engagement positions. Suitably, the number of gear teeth isfrom 2 to 20, preferably from 3 to 10.

In one aspect, the gear engagement positions are equally spaced (e.g.equidistantly spaced) and the gear teeth are offset (e.g.non-equidistantly spaced) relative thereto. Such offset arrangementmaximises the number of effective individual gear positions which arecapable of definition. An example of this aspect, is the Vernier springarrangement described herein.

In another aspect, the gear engagement positions are also equally spaced(e.g. equidistantly spaced) and the gear teeth are located on a wobblingelement capable of wobbling the gear teeth to plural offset (e.g.non-equidistantly spaced) positions. Such a wobbling offset arrangementalso maximises the number of effective individual gear positions whichare capable of being defined. An example of this aspect, is the wobblingwheel arrangement described herein.

In aspects, the clutch means is non-integral with either of the liddriving means or the indexing means, but forms a separateinterconnecting component.

Suitably, the gearing surface comprises a gear wheel. As used herein,the term gear wheel encompasses, for example, a wheel, spindle or spool.

Suitably, the gear teeth may be arranged to be in ratchet form (i.e.enabling movement in one direction only).

Suitably, the gearing surface and gear teeth are in biased (e.g. sprung)engagement.

In another aspect, the lid driving means comprises a wheel on which thelid sheet is wound up, said wheel having a winding surface whichdecreases in diameter when tension in the lid sheet increases.

Suitably, said wheel comprises a plurality of resiliently flexible armseach extending therefrom at an angle with respect to a radius. Theleading end of the lid sheet is looped over one of said resilientlyflexible arms to secure the lid sheet to the wheel initially.

Alternatively, the lid driving means comprise a mangle. The lid sheetpasses through two rotating wheels which act as a mangle and is grippedat the point of contact with the wheels. The used portion of the lidsheet is collected in a chamber after it has passed through the mangle.

Alternatively, the lid driving means comprise a roller. Suitably, saidroller is composed of a polymeric rubber and is positioned next to aguide wall. Suitably, said roller has a smooth surface. Alternativelysaid roller has a knurled surface. The roller grips the lid sheet as itpasses from the point at which it is separated from the base sheetthrough the space between the roller and the guide wall and the usedportion of the lid sheet is then collected in a chamber. The roller hasthe advantage over the mangle described above in that a greater degreeof contact between the roller wheel and the lid sheet occurs—the lidsheet is squeezed through the roller and may pass around about ⅓ of theroller wheel. This provides a higher level of grip and pulling forcethan with a mangle. The force required to turn the roller is constantthroughout the use of the device and does not vary according to how muchof the lid sheet has been peeled away from the base sheet. This is incontrast to the wheel described above where the forces required to turnthe wheel may vary due to the fact that the lid sheet is wound aroundthe wheel. The lid sheet is not wound around the roller. The roller alsohas the advantage that the lid sheet does not have to be looped aroundor fixed to the roller before use of the device, therefore simplifyingassembly of the device and reducing costs.

In a further aspect, the lid driving means comprise a spiked wheel. Asthe spiked wheel turns, the lid sheet is pulled over it and the spikesperforate parts of the lid sheet to improve the grip on the lid sheet.The lid sheet then passes out into a chamber where it collects.

In a further aspect, the lid driving means comprise a clamp system. Theclamp system comprises at least one angled spring which is pivotable atone end and grips the lid sheet at the other end. The clamp system ismoved in the direction that the lid sheet is to be pulled and grips thelid sheet, pulling it and therefore peeling it away from the base sheet.The clamp system is then moved back to its rest position. This resultsin the spring pivoting and clamping the lid sheet, therefore preventingthe lid sheet from being further peeled from the base sheet.

In an alternative aspect, the used portion of the lid sheet may bepassed around rollers and fed back onto the used portion of the basesheet after the medicament has been accessed to join back onto the basesheet. The lid sheet may be coated with a sticky substance to aidresealing. The use of this mechanism saves space as the used portions ofthe blister strip will be collected in the same area.

In a further aspect, the coil comprising the unused medicament strip maybe surrounded by a constant force spring. Alternatively the coilcomprising the unused medicament strip may be surrounded by anelastomeric band or band comprising a contractible material. Theconstant force spring, elastomeric band or band comprising acontractible material contracts as the coil reduces in size.

Suitably, said peeling means additionally comprise a guide for guidingthe lid sheet and base sheet along separate paths at the openingstation. The lid sheet is passed around the guide portion onto the liddriving means.

Suitably, the guide comprises a structure fixed in position in thecassette.

Alternatively, the guide comprises a roller mechanism. The lid sheet isfed over the rollers onto the lid driving means.

In one aspect, the lid driving means and/or the index ratchet areoperated by an electronic drive system. The electronic drive system mayalso be used in conjunction with a mechanical drive system. Theelectronic drive system may include a DC motor.

The electronic drive means typically comprises a motor, preferably anelectrically-powered motor. The motor may provide linear or rotarydrive, but in general, rotary motors are most suitable. The motor mayfor example, comprise a DC electric motor, a piezoelectric (PZ) motor,an ultrasonic motor, a solenoid motor or a linear motor. Preferably, theelectronic drive system comprises a DC motor, a PZ motor or anultrasonic motor.

The use of ultrasonic motors is particularly preferred since they offeradvantages over conventional motors in terms of weight, size, noise,cost and torque generated. Ultrasonic motors are well known in the artand are commercially available (e.g. BMSTU Technological CooperationCentre Ltd, Moscow, Russia; Shinsei Corporation, Tokyo, Japan).

Ultrasonic motors do not use coils or magnets but comprise apiezoelectric ceramic stator which drives a coupled rotor. The statorgenerates ultrasonic vibrations which in turn causes rotation of therotor. While regular DC motors are characterised by high speed and lowtorque, requiring reduction gearing to increase torque, ultrasonicmotors attain low speed and high torque, thus eliminating the need forreduction gearing. Furthermore, these motors are lightweight andcompact, lacking coils and magnets, and are noiseless as the ultrasonicfrequencies used are not audible to the human ear.

Suitably, the dispenser further comprises actuating means for actuatingsaid electronic drive system. Said actuating means may take the form ofa switch, push-button, or lever.

Suitably, the internal mechanism additionally comprises a first chamberin which the strip is initially housed and from which it is dispensedand a second chamber to receive the used portion of the base sheet afterit has been indexed and separated from the lid sheet.

Suitably, said first chamber and said second chamber are separated by awall.

Suitably, said wall is movable to adjust the size of said first andsecond chambers.

Suitably, the wall is pivotally mountable. Alternatively, the wall isslidably mountable.

Suitably, the wall is flexible to allow changes in the relative size ofsaid first and second chambers.

Suitably, the internal mechanism further comprises a third chamber toreceive the used portion of the lid sheet and a fourth chamber whichhouses the index ratchet. The fourth chamber may communicate via a slit,which in turn extends upwardly within a mouthpiece and communicates withair inlets.

Suitably, the internal mechanism additionally comprises a crushing wheelto crush the medicament pockets after the medicament has been removedfrom them. The crushing wheel therefore reduces the space which the usedportion of the base sheet takes up.

Typically, the internal mechanism for accessing said medicamentcontained within said medicament carrier is housed within a cassette.

According to another aspect of the present invention there is provided amedicament dispenser for dispensing medicament comprising: a body; aholder, shaped to fit within said body and movable relative to saidbody; and receivable by said holder, a cassette containing saidmedicament carrier.

Suitably, movement of the holder relative to the body results inmovement of the cassette between a first position and a second positionsuch that the cassette is reversibly removable from the holder when thecassette is in the second position.

Suitably, the first position comprises a dispensing position. Preferablythe second position comprises a non-dispensing position. The cassette istherefore only removable from the holder when the cassette is in thenon-dispensing position.

Suitably, the holder and body include attaching means to attach theholder to the body. Preferably, said attaching means comprise a snap fitmechanism. Preferably, said snap fit mechanism comprises a pin and holesystem.

Suitably, the holder is pivotally movable relative to the body.

Alternatively, the holder is rotationally movable relative to the body.

Suitably, the holder additionally comprises a stop to limit movement ofthe holder relative to the body. The stop abuts against the edge of thebody at two points when it is rotated. At these points the holder may bedesigned to click into place. Therefore when the stop abuts one bodyedge then it is clicked into the dispensing position and when the stopabuts the other body edge then it is clicked into the non-dispensingposition.

Alternatively, the holder is slidably movable relative to the body.

Suitably, the holder additionally comprises a catch to retain thecassette. The catch may for example comprise a sprung pin which fitsinto a hole or an integral catch which deforms when pressed allowingremoval of the cassette.

Suitably, the catch is child resistant. Child resistance may be realisedby having a system which forces the user to perform two actions at onceto remove the cassette. Other features of the catch may include shock orimpact resistance, the ability to lock the catch and orientationfeatures to ensure that the cassette can only be inserted one way. Thecatch should also be easy to manufacture and assemble, be robust, becomposed of a minimal number of components and intrude minimally intothe space into which the cassette is inserted.

Suitably, the holder includes guide means to guide the cassette into theholder. Preferably said guide means comprise guide rails. Alternativelythe guide means comprise grooves, indentations or other shaping orsurface details to define a ‘lock and key’ relationship between theholder and the cassette. Colour guides, arrows and any other surfacemarkings may also be employed.

Suitably, the cassette additionally comprises an indexing lever. Theindexing lever has a finger tab located outside the body of thecassette. The rest of the indexing lever is located within the cassette.The indexing lever may have teeth at its tail end and/or teeth along itsmid portion.

Suitably, the cassette additionally comprises a mouthpiece.

Suitably, said mouthpiece is extendable. The mouthpiece extends as thecassette and holder are moved from the non-dispensing position to thedispensing position.

Alternatively, the mouthpiece is retractable. The mouthpiece retracts asthe cassette and holder are moved from the dispensing position to thenon-dispensing position.

In one aspect, the mouthpiece is telescopic. Alternatively, themouthpiece is fixed.

The medicament dispenser may also be designed for nasal inhalation of apowdered medicament and may therefore incorporate a nosepiece as analternative to a mouthpiece. If the medicament is in solid form, thedispenser may incorporate an exit channel for tablet release.

Suitably, the body covers the mouthpiece and indexing lever when thecassette is in the non-dispensing position. This avoids the need for aseparate cover and protects the mouthpiece from the ingress of dirt andcontaminants during storage.

Suitably, the cassette additionally comprises a raised portion to fitagainst the holder. The raised portion is located at the opposite end ofthe cassette to the mouthpiece/nosepiece/exit and indexing lever andprevents the incorrect insertion of the cassette into the holder sinceit is too wide to fit into the holder. The raised portion is shaped suchthat it fits against a cut away part of the holder. Preferably, saidraised portion includes a section which is raised to define a gripportion.

Suitably, at least a portion of the holder and body are shaped for easeof grip by the user.

Suitably, operation of the device may be performed with one hand.

Suitably, the medicament dispenser comprises an actuation or dosecounter for counting the number of actuations of the indexing lever orreleases of dose from the cassette.

The dose counter may count the number of doses left to be taken or thenumber of doses taken.

Suitably, said dose counter is electronic. Alternatively, said dosecounter is mechanical.

Suitably, said dose counter is located within the cassette.Alternatively, the dose counter is external to the cassette.

Alternatively, the blister strip has printed numbers on it correspondingto the doses in the pockets. Preferably, said printed numbers arevisible through a window in the cassette.

The device may be assembled as follows. The holder is snap fitted intothe body. The cassette is assembled separately. The body of the cassetteis formed, preferably in two sections with any necessary spindles orintegral components formed into the base. Individual components such asindexing wheels, lid winding mechanisms, guide portions etc are thenassembled into the base. Finally the medicament containing blister strip(or other suitable medicament carrier) may be inserted into thecassette. This may be wound into the device before the lid is attachedto the cassette and the cassette sealed. Alternatively, the cassette maybe formed completely apart from a hole left in its side for insertion ofthe blister strip or medicament carrier. The hole may then be sealed tocomplete the cassette. This second method of inserting the medicamentcarrier into the device has the advantage that it is much simpler.

Suitably, the medicament dispenser additionally comprises an electronicdata management system. The electronic data management system hasinput/output capability and comprises a memory for storage of data; amicroprocessor for performing operations on said data; and a transmitterfor transmitting a signal relating to the data or the outcome of anoperation on the data.

Suitably, the electronic data management system is arranged to beresponsive to or activated by the voice of a user. Thus, for example thesystem may be switched on or off in response to a voice command.

The electronic data management system may be integral with the body.Alternatively, the electronic data management system forms part of abase unit which is reversibly associable with the body.

Suitably, the medicament dispenser additionally comprises a data inputsystem for user input of data to the electronic data management system.Preferably, the data input system comprises a man machine interface(MMI) preferably selected from a keypad, voice recognition interface,graphical user interface (GUI) or biometrics interface.

Energy may be conserved by a variety of means to enable the device tooperate for longer on a given source of energy, such as a battery.Energy conservation or saving methods have additional advantages interms of reducing the size requirements of the power source (e.g.battery) and thus the weight and portability of the medicamentdispenser.

A variety of energy saving methods are available which generally involvereducing power consumption. One such method is to use a clock or timercircuit to switch the power on and off at regular or predeterminedintervals. In another method the system can selectively switch on/offspecific electronic devices, such as visual display units or sensors, inorder to power these devices only when they are required to perform aparticular sequence of events. Thus different electronic devices may beswitched on and off at varying intervals and for varying periods undercontrol of the system. The power sequencing system may also respond to asensor, such as a motion or breath sensor, which is activated on use ofthe device.

Low power or “micropower” components should be used within theelectronics where possible and if a high power device is required for aparticular function this should be put into a low power standby mode orswitched off when not required. Similar considerations apply in theselection of transducers. Operation at low voltage is desirable sincepower dissipation generally increases with voltage.

For low power digital applications complementary metal oxidesemi-conductor (CMOS) devices are generally preferred and these may bespecially selected by screening for low quiescent currents. Clock speedsof processors and other logic circuits should be reduced to the minimumrequired for computational throughput as power consumption increaseswith frequency. Supply voltages should also be kept at minimal valuesconsistent with reliable operation because power dissipation in charginginternal capacitance's during switching is proportional to the square ofthe voltage. Where possible, supply voltages should be approximately thesame throughout the circuit to prevent current flowing through inputprotection circuits. Logic inputs should not be left floating andcircuits should be arranged so that power consumption is minimised inthe most usual logic output state. Slow logic transitions areundesirable because they can result in relatively large class-A currentsflowing. Resistors may be incorporated in the power supply to individualdevices in order to minimise current in the event of failure.

In some control applications, devices that switch between on and offstates are preferred to those that allow analog (e.g. linear) controlbecause less power is dissipated in low resistance on states and lowcurrent off states. Where linear components are used (e.g. certain typesof voltage regulators) then types with low quiescent currents should beselected. In some circuit configurations it is preferable to useappropriate reactive components (i.e. inductors and capacitors) toreduce power dissipation in resistive components.

Suitably, the system additionally comprises a visual display unit fordisplay of data from the electronic data management system to the user.The display may for example, comprise a screen such as an LED or LCDscreen. More preferably the visual display unit is associable with thebody of the medicament dispenser.

Suitably, the medicament dispenser additionally comprises a datalink forlinking to a local data store to enable communication of data betweenthe local data store and the electronic data management system. Thedatastore may also comprise data management, data analysis and datacommunication capability.

The datastore may itself form part of a portable device (e.g. a handhelddevice) or it may be sized and shaped to be accommodated within thepatient's home. The datastore may also comprise a physical storage areafor storage of replacement cassettes. The datastore may further comprisea system for refilling medicament from a reservoir of medicament productstored therewithin. The datastore may further comprise an electricalrecharging system for recharging any electrical energy store on themedicament dispenser, particularly a battery recharging system.

The datalink may for example enable linking with a docking station, apersonal computer, a network computer system or a set-top box by anysuitable method including a hard-wired link, an infra red link or anyother suitable wireless communications link.

Suitably, the medicament dispenser additionally comprises an actuationdetector for detecting actuation of the dispensing mechanism whereinsaid actuation detector transmits actuation data to the electronic datamanagement system.

The medicament dispenser may additionally comprise a safety mechanism toprevent unintended multiple actuations of the dispensing mechanism. Thepatient is thereby protected from inadvertently receiving multiple dosesof medicament in a situation where they take a number of short rapidbreaths. More preferably, the safety mechanism imposes a time delaybetween successive actuations of the release means. The time delay istypically of the order of from three to thirty seconds.

Suitably, the medicament dispenser additionally comprises a releasedetector for detecting release of medicament from the cassette, whereinsaid release detector transmits release data to the electronic datamanagement system.

Suitably, the medicament dispenser additionally comprises a shakedetector for detecting shaking of the medicament container (e.g. priorto actuation of the dispensing mechanism), wherein said shake detectortransmits shake data to the electronic data management system.

Suitably, any actuation detector, release detector, or shake detectorcomprises a sensor for detecting any suitable parameter such asmovement. Any suitable sensors are envisaged including the use ofoptical sensors. The release detector may sense any parameter affectedby release of the medicament such as pressure, temperature, sound,moisture, carbon dioxide concentration and oxygen concentration.

Suitably, the medicament dispenser additionally comprises a breathtrigger for triggering the dispensing mechanism, said breath triggerbeing actuable in response to a trigger signal from the electronic datamanagement system. Preferably, the electronic data management systemincludes a predictive algorithm or look-up table for deriving from thebreath data when to transmit the trigger signal. For example, areal-time analysis of the patient breath waveform may be made and thetrigger point derived by reference to that analysed waveform.

Suitably, the electronic data management system includes a predictivealgorithm or look-up table for calculating the optimum amount ofmedicament to dispense.

Suitably, the memory on the electronic data management system includes adose memory for storing dosage data and reference is made to the dosememory in calculating the optimum amount of medicament to dispense.

Suitably, the medicament dispenser additionally comprises a selector forselecting the amount of medicament to dispense from said dispensingmechanism. In one aspect, the selector is manually operable. In anotheraspect, the selector is operable in response to a signal from thetransmitter on the electronic data management system.

Suitably, the medicament dispenser comprises in association with a bodyor housing thereof, a first transceiver for transmitting and receivingdata and in association with the medicament container, a secondtransceiver for transmitting and receiving data, wherein data istransferable in two-way fashion from the first transceiver to the secondtransceiver. The data is preferably in digital form and suitable fortransfer by electronic or optical means. A medicament dispenser of thisgeneral type is described in pending UK Patent Application No.0020538.5.

One advantage of embodiments of this type is the ability to store manytypes of information in different parts of the memory structure of thetransceivers. The information is furthermore stored in a form which isreadily and accurately transferable. The information could for example,include manufacturing and distribution compliance information written tothe memory at various points in the manufacturing or distributionprocess, thereby providing a detailed and readily accessible producthistory of the dispenser. Such product history information may, forexample, be referred to in the event of a product recall. The complianceinformation could, for example, include date and time stamps. Theinformation could also include a unique serial number stored inencrypted form or in a password protectable part of the memory whichuniquely identifies the product and therefore may assist in thedetection and prevention of counterfeiting. The information could alsoinclude basic product information such as the nature of the medicamentand dosing information, customer information such as the name of theintended customer, and distribution information such as the intendedproduct destination.

On loading or reloading the medicament dispenser with a cassette thesecond transceiver may, for example, read the unique serial number,batch code and expiry date of the medicament and any other informationon the second transceiver. In this way the nature and concentration ofthe medicament, together with the number of doses used or remainingwithin the cassette, may be determined. This information can bedisplayed to the patient on a visual display unit. Other information,such as the number of times the medicament dispenser has been reloadedwith a cassette, may also be displayed.

Similarly, should the cassette be removed from the holder before thesupply of medicament is exhausted, the same data can be read from thesecond transceiver and the number of doses remaining or used determined.Other information, such as the date and time of administration of thedrug, or environmental exposure data such as the minimum/maximumtemperatures or levels of humidity the cassette has been exposed to, mayalso be read and displayed to the user.

In the event that the supply of medicament within the container becomesexhausted, or that the shelf life of the medicament has expired, or thatthe first transceiver does not recognise the batch code on the secondtransceiver, activation of the dispenser may be prevented to safeguardthe user. Activation may also be prevented if the medicament has beenexposed to extreme environmental conditions for periods outwith themanufacturer's guidelines.

Data may be transferred to and from any transceiver during the period ofuse of the medicament dispenser by the patient. For example, themedicament dispenser may include an electronic data management systemhaving various sensors associated therewith. Any data collected by thesensors or from any data collection system associated with theelectronic data management system including a clock or other date/timerecorder is transferable.

Data may be transferred each time the patient uses the device. Oralternatively, data may be stored in a database memory of the electronicdata management system and periodically downloaded to any transceiver.In either case, a history of the usage of the device may be built up inthe memory of a transceiver.

In one embodiment herein, a history of the usage of the medicamentdispenser is transferred to the second transceiver. When the blisterstrip in the cassette is exhausted it is exchanged by the patient for anew refill cassette. At the point of exchange, which will typicallyoccur at the pharmacy, data may be transferred from the exhaustedcassette to the refill and vice-versa. Additionally, usage history datamay be read from the refill and transferred to a healthcare datamanagement system for example comprising a network computer system underthe control of a healthcare data manager.

Methods are envisaged herein whereby the patient is given some sort ofreward for returning the refill and making available the data comprisedwithin the second transceiver. Methods are also envisaged herein wherebythe healthcare data manager is charged for either receipt of the datafrom the second transceiver or for its use for commercial purposes. Anyrewards or charging may be arranged electronically. The methods may beenabled by distributed or web-based computer network systems in whichany collected data is accessible through a hub on the network. The hubmay incorporate various security features to ensure patientconfidentiality and to allow selective access to information collecteddependent upon level of authorisation. The level of user authorisationmay be allocated primarily to safeguard patient confidentiality. Beyondthis the level of user authorisation may also be allocated on commercialterms with for example broader access to the database being authorisedin return for larger commercial payments.

Suitably, the first and second transceiver each comprise an antenna orequivalent for transmitting or receiving data and connecting thereto amemory. The memory will typically comprise an integrated circuit chip.Either transceiver may be configured to have a memory structure whichallows for large amounts of information to be stored thereon. The memorystructure can be arranged such that parts of the memory are read-only,being programmed during/after manufacture, other parts are read/writeand further parts are password protectable. Initial transfer ofinformation (e.g. on manufacture or one dispensing) to or from anytransceiver can be arranged to be readily achievable by the use of areader which is remote from the medicament dispenser, thereby minimisingthe need for direct product handling. In further aspects, the reader canbe arranged to simultaneously read or write to the memory of multipletransceivers on multiple medicament dispensers.

A suitable power source such as a battery, clockwork energy store, solarcell, fuel cell or kinetics-driven cell will be provided as required toany electronic component herein. The power source may be arranged to berechargeable or reloadable.

Suitably, data is transferable in two-way fashion between the first andsecond transceiver without the need for direct physical contacttherebetween. Preferably, data is transferable wirelessly between thefirst and second transceiver.

Suitably, the first transceiver is an active transceiver and the secondtransceiver is a passive transceiver. The term active is used to meandirectly-powered and the term passive is used to meanindirectly-powered.

Suitably, the second transceiver comprises a label or tag comprising anantenna for transmitting or receiving energy; and an integrated circuitchip connecting with said antenna, and the first transceiver comprises areader for said label or tag. In this case the label or tag is a passivetransceiver and the reader is an active transceiver. Preferably, thereader will not need to be in direct contact with the tag or label toenable the tag or label to be read. The tag may be used in combinationand/or integrated with other traditional product labelling methodsincluding visual text, machine-readable text, bar codes and dot codes.

Suitably, the integrated circuit chip has a read only memory area, awrite only memory area, a read/write memory area or combinationsthereof.

Suitably, the integrated circuit chip has a one-time programmable memoryarea. More preferably, the one-time programmable memory area contains aunique serial number.

Suitably, the integrated circuit chip has a preset memory areacontaining a factory preset, non-changeable, unique data item. Thepreset memory item is most preferably in encrypted form.

Suitably, the integrated circuit chip has plural memory areas thereon.Suitably, any memory area is password protected.

Suitably, any memory area contains data in encrypted form. Electronicmethods of checking identity, error detection and data transfer may alsobe employed.

In one aspect, the integrated circuit has plural memory areas thereonincluding a read only memory area containing a unique serial number,which may for example be embedded at the time of manufacture; aread/write memory area which can be made read only once information hasbeen written thereto; and a password protected memory area containingdata in encrypted form which data may be of anti-counterfeiting utility.

Suitably, the tag is on a carrier and the carrier is mountable on thebody or holder of the medicament dispenser or on the cassette.

In one aspect, the carrier is a flexible label. In another aspect, thecarrier is a rigid disc. In a further aspect, the carrier is arectangular block. In a further aspect, the carrier is a collar ringsuitable for mounting to the neck of an aerosol container. Other shapesof carrier are also envisaged.

Suitably, the carrier is mouldable or weldable to the cassette orhousing. Suitably, the carrier encases the tag. More preferably, thecarrier forms a hermetic seal for the tag.

In one aspect, the carrier comprises an insulating material such as aglass material or, a paper material or an organic polymeric materialsuch as polypropylene. Alternatively, the carrier comprises a ferritematerial.

The energy may be in any suitable form including ultrasonic, infrared,radiofrequency, magnetic, optical and laser form. Any suitable channelsmay be used to channel the energy including fibre optic channels.

In one aspect, the second transceiver comprises a radiofrequencyidentifier comprising an antenna for transmitting or receivingradiofrequency energy; and an integrated circuit chip connecting withsaid antenna, and the first transceiver comprises a reader for saidradiofrequency identifier. In this case the radiofrequency identifier isa passive transceiver and the reader is an active transceiver. Anadvantage of radiofrequency identifier technology is that the readerneed not be in direct contact with the radiofrequency identifier tag orlabel to be read.

The radiofrequency identifier can be any known radiofrequencyidentifier. Such identifiers are sometimes known as radiofrequencytransponders or radiofrequency identification (RFID) tags or labels.Suitable radiofrequency identifiers include those sold by PhillipsSemiconductors of the Netherlands under the trade marks Hitag and Icode,those sold by Amtech Systems Corporation of the United States of Americaunder the trade mark Intellitag, and those sold by Texas Instruments ofthe United States of America under the trade mark Tagit.

Suitably, the antenna of the RFID tag is capable of transmitting orreceiving radiofrequency energy having a frequency of from 100 kHz to2.5 GHz. Preferred operating frequencies are selected from 125 kHz,13.56 MHz and 2.4 GHz.

In one aspect, the second transceiver comprises a magnetic label or tagcomprising an antenna for transmitting or receiving magnetic fieldenergy; and an integrated circuit chip connecting with said antenna, andthe first transceiver comprises a reader for said magnetic label or tag.In this case the magnetic label or tag is a passive transceiver and thereader is an active transceiver.

A suitable magnetic label or tag comprises plural magnetic elements inmutual association whereby the magnetic elements move relative to eachother in response to an interrogating magnetic field. A magnetic labelor tag of this type is described in U.S. Pat. No. 4,940,966. Anothersuitable magnetic label or tag comprises a magnetorestrictive elementwhich is readable by application of an interrogating alternatingmagnetic field in the presence of a magnetic bias field which results inresonance of the magnetorestrictive elements at different predeterminedfrequencies. A magnetic label of this type is described in PCT PatentApplication No. WO92/12402. Another suitable magnetic label or tagcomprising plural discrete magnetically active regions in a linear arrayis described in PCT Patent Application No. WO96/31790. Suitable magneticlabels and tags include those making use of Programmable MagneticResonance (PMR) (trade name) technology.

In another aspect, the second transceiver comprises a microelectronicmemory chip and the first transceiver comprises a reader for saidmicroelectronic memory chip. The microelectronic memory chip maycomprise an Electrically Erasable Programmable Read Only Memory (EEPROM)chip or a SIM card-type memory chip. In this case the microelectronicmemory chip is a passive transceiver and the reader is an activetransceiver.

Any transceiver herein, particularly a passive transceiver may bemounted on or encased within any suitable inert carrier. The carrier maycomprise a flexible sheet which may in embodiments be capable ofreceiving printed text thereon.

In one aspect, the first transceiver is integral with the body such thata single unit is comprised. The first transceiver may for example beencased within or moulded to the body.

In another aspect, the first transceiver forms part of a base unit whichis reversibly associable with the body. The base unit may for example,form a module receivable by the body such as a snap-in module.

Suitably, the medicament dispenser additionally comprises a communicatorfor wireless communication with a network computer system to enabletransfer of data between the network computer system and the electronicdata management system. Dispensers employing such communicators aredescribed in pending PCT Applications Nos. PCT/EP00/09291 (PG3786),PCT/EP00/09293 (PG4029) and PCT/EP00/09292 (PG4159). Preferably, thecommunicator enables two-way transfer of data between the networkcomputer system and the electronic data management system.

Suitably, the data is communicable between the network computer systemand the electronic data management system in encrypted form. Allsuitable methods of encryption or partial encryption are envisaged.Password protection may also be employed. Suitably, the communicatoremploys radiofrequency or optical signals.

In one aspect, the communicator communicates via a gateway to thenetwork computer system. In another aspect, the communicator includes anetwork server (e.g. a web server) such that it may directly communicatewith the network.

In a further aspect, the communicator communicates with the gateway viaa second communications device. Preferably, the second communicationsdevice is a telecommunications device, more preferably a cellular phoneor pager. Preferably, the communicator communicates with the secondcommunications device using spread spectrum radiofrequency signals. Asuitable spread spectrum protocol is the Bluetooth (trade mark) standardwhich employs rapid (e.g. 1600 times a second) hopping between pluralfrequencies (e.g. 79 different frequencies). The protocol may furtheremploy multiple sending of data bits (e.g. sending in triplicate) toreduce interference.

In one aspect, the network computer system comprises a public accessnetwork computer system. The Internet is one suitable example of apublic access network computer system, wherein the point of accessthereto can be any suitable entrypoint including an entrypoint managedby an Internet service provider. The public access network computersystem may also form part of a telecommunications system, which mayitself be either a traditional copper wire system, a cellular system oran optical network.

In another aspect, the network computer system comprises a privateaccess network computer system. The private access network system mayfor example, comprise an Intranet or Extranet which may for example, bemaintained by a health service provider or medicament manufacturer. Thenetwork may for example include password protection; a firewall; andsuitable encryption means.

Preferably, the communicator enables communication with a user-specificnetwork address in the network computer system.

The user-specific network address may be selected from the groupconsisting of a web-site address, an e-mail address and a file transferprotocol address. Preferably, the user-specific network address isaccessible to a remote information source such that information fromsaid remote information source can be made available thereto. Morepreferably, information from the user-specific network address can bemade available to the remote information source.

In one aspect, the remote information source is a medicament prescriber,for example a doctors practice. Information transferred from themedicament prescriber may thus, comprise changes to prescriptiondetails, automatic prescription updates or training information.Information transferred to the medicament prescriber may comprisecompliance information, that is to say information relating to thepatient's compliance with a set prescribing programme. Patientperformance information relating for example, to patient-collecteddiagnostic data may also be transferred to the medicament prescriber.Where the dispenser is an inhaler for dispensing medicament for therelief of respiratory disorders examples of such diagnostic data wouldinclude breath cycle data or peak flow data.

In another aspect, the remote information source is a pharmacy.Information transferred from the pharmacy may thus, comprise informationrelating to the medicament product. Information sent to the pharmacy maythus include prescription requests which have been remotelypre-authorised by the medicament prescriber.

In a further aspect, the remote information source is an emergencyassistance provider, for example a hospital accident and emergencyservice or an emergency helpline or switchboard. The information maythus, comprise a distress or emergency assist signal which requestsemergency assistance.

In a further aspect, the remote information source is a manufacturer ofmedicament or medicament delivery systems. Information transferred tothe system may thus, comprise product update information. The system mayalso be configured to feed information back to the manufacturer relatingto system performance.

In a further aspect, the remote information source is a researchestablishment. In a clinical trial situation, information may thus betransferred relating to the trial protocol and information relating topatient compliance fed back to the research establishment.

In a further aspect, the remote information source is an environmentalmonitoring station. Information relating to weather, pollen counts andpollution levels may thus be made accessible to the system.

Suitably, the medicament dispenser additionally comprises a geographicpositioning system such as a global positioning system or a system whichrelies on the use of multiple communications signals and a triangulationalgorithm.

The medicament may comprise a capsule, pellet or tablet. Alternatively,the medicament may be in powdered form. Preferably, when in powderedform the medicament comprises a drug. Preferably the drug is selectedfrom the group consisting of albuterol, salmeterol, fluticasonepropionate and beclomethasone dipropionate and salts or solvates thereofand any combination thereof. Preferably said combination comprisessalmeterol xinafoate and fluticasone propionate.

Suitably, the powdered medicament additionally comprises an excipient.Suitably, said excipient is a sugar.

In yet another aspect, the invention provides a kit of parts comprisinga cassette as described supra, a holder for a cassette and a bodywherein the holder is shaped to fit within said body and may be movablerelative to said body.

In a further aspect, the invention provides a body and holder for use inthe medicament dispenser described supra.

In still a further aspect, the invention provides a cassette for use inthe medicament dispenser described supra.

In yet another aspect, the invention provides the use of a medicamentdispenser as described supra.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described with reference to the accompanyingdrawings in which:

FIG. 1 a shows a cassette housing an internal mechanism in accordancewith one aspect of the invention;

FIG. 1 b shows a base unit of a medicament dispenser onto which thecassette of FIG. 1 a is receivable;

FIG. 2 shows a perspective view of a medicament carrier in accordancewith the present invention;

FIG. 3 a shows an asymmetric cassette comprising an internal mechanismin accordance with another aspect of the invention;

FIG. 3 b shows a round cassette comprising an internal mechanism inaccordance with another aspect of the invention;

FIG. 4 shows a perspective view of a medicament dispenser according tothe invention with the cassette removed from the holder and the body;

FIG. 5 a shows a perspective view of a refill cassette comprising aninternal mechanism according to a further aspect of the invention; and

FIG. 5 b shows the refill cassette of FIG. 5 a in exploded view.

DETAILED DESCRIPTION OF THE DRAWINGS

Referring now to the Figures, the internal mechanism according to oneaspect of the invention is illustrated housed in a cassette 100 in FIG.1 a. The cassette 100 is sized and shaped for receipt by base unit 130shown in FIG. 1 b.

Medicament carrier in the form of an elongate blister strip 102 (seealso FIG. 2) is coiled in chamber 104 and fed about a guide wall 106 tothe opening station 108 and beak 110. After the blister pack 102 ispeeled into separate lid sheet 112 and base sheet 114, the lid sheet 112is fed to a lid spool 116 in the lid spool chamber 116 a, and the basesheet 114 to a base spool 118 in the base spool chamber 118 a.

An index ratchet 120 prevents movement of the blister strip 102. A nose122 on the index ratchet 120 rests adjacent a medicament pocket 124 onthe strip 102 hence halting further progression of the strip 102 throughthe mechanism.

The base unit 130 is shown in FIG. 1 b and houses the index lever 132and the lid spool driving means 134. The index lever 132 has a leverratchet 136 that engages with an index gear 138 which in turn engagesand drives the lid spool drive gear 140 and the base spool drive gear142. Thus, displacement of the index lever 132 results in rotation ofthe lid spool 116 and base spool 118 in opposite directions to pullapart the lid sheet 112 and the base sheet 114. The lever ratchet 136and a non-return ratchet 144 prevent movement of the index gear 138 inthe other direction. The index lever 132 also has a cam surface 150.

To actuate the medicament dispenser, the index lever 132 is displacedand the pin 120 a of the index ratchet 120 follows the cam surface 150thereof to move the index ratchet 120 away from already-opened pocket124 of the strip 102 to its ‘release position’. In consequence, strip102 is released for further travel within the dispenser 100. The lidspool driving means 134 is also thereby freed to act such as to peel thelid sheet 112 about beak 110 to open the next pocket 124 a to enable therelease of medicament therefrom.

As the index lever 132 returns to rest, the cam surface 150 urges theindex ratchet 120 back to its ‘locked position’ whereby the strip 102 isprevented from further movement.

As the lid spool 116 receives the peeled lid sheet 112, the diameter ofthe outer winding surface 158 gradually increases. In order to ensurethat the same dose is dispensed every time, that is, only one blisterpack is opened for every actuation of the dispenser, a lever stop (notshown) is fitted which correspondingly shortens the amount the lid spooldrive gear 140 is rotated to allow for the increase in diameter of thelid spool winding surface 158. Hence, the medicament carrier is indexedby the same amount each time and a uniform, consistent dose is alwaysdispensed.

Chamber 104 housing the unused blister strip 102 and the base spoolchamber 118 a, are separated by a wall 170. The wall 170 is movable toadjust the relative size of the chambers 104, 118 a. The wall may bepivotally mountable or slidably mountable. In this case, the wall 170 isflexible.

The wall 170 additionally comprises at least one brush (not shown)located along its top or bottom side which brush against the top andbottom surfaces of the inside of the cassette. The brushes may act toclose off the chamber from the rest of the body of the cassette and toprevent any loose powder from entering the rest of the cassette. Loosepowder may enter the chambers from the used portion of the blister stripif the patient indexes the strip by pressing the lever when they do notintend to take a dose or when they fail to inhale all the powder.

FIG. 2 shows a medicament carrier 200 in accord with the presentinvention. The medicament carrier comprises a flexible strip 202defining a plurality of pockets 204, 206, 208 each of which contains adose of medicament which can be inhaled, in the form of powder.

The strip comprises a base sheet 210 in which blisters are formed todefine the pockets 204, 206, 208 and a lid sheet 212 which ishermetically sealed to the base sheet except in the region of theblisters in such a manner that the lid sheet 212 and the base sheet 210can be peeled apart. The sheets 210, 212 are sealed to one another overtheir whole width except for the leading end portions 214, 216 wherethey are preferably not sealed to one another at all. The lid 212 andbase 210 sheets are each preferably formed of a plastics/aluminiumlaminate and are preferably adhered to one another by heat sealing.

The strip 202 is shown as having elongate pockets 204, 206, 208 whichrun transversely with respect to the length of the strip 202. This isconvenient in that it enables a large number of pockets 204, 206, 208 tobe provided in a given strip length. The strip may, for example, beprovided with sixty or one hundred pockets but it will be understoodthat the strip may have any suitable number of pockets.

FIGS. 3 a and 3 b illustrate variations of the cassette of FIG. 1 a, inwhich a corresponding mechanism is accommodated within differentlyshaped cassette housings. FIG. 3 b shows an asymmetric variation andFIG. 3 c shows a round cassette. The cassette housings of FIGS. 3 a and3 b will engage with base units (not shown) of correspondingshape/configuration and having the general internal features of FIG. 1b.

For clarity, only the principal features of the internal mechanismfeatures of the variations of FIGS. 3 a and 3 b are labelled. Thecassette housing 300 houses medicament carrier blister strip 302 (seealso FIG. 2) coiled in a chamber 304 and fed about a guide wall 306 tothe opening station 308 and beak 310. After the blister pack 302 ispeeled into separate lid sheet 312 and base sheet 314, the lid sheet 312is fed to a lid spool 316 in the lid spool chamber 316 a, and the basesheet 314 to a base spool 318 in the base spool chamber 318 a.

In the rest position, index ratchet 320 is in its ‘locked position’ inwhich it prevents movement of the blister strip 302. A nose 322 on theindex ratchet 320 rests adjacent an already-opened medicament pocket 324on the strip 302 hence halting further progression of the strip 302through the mechanism. The index ratchet 320 is pivotally movable to a‘release position’ in which it no longer contact the pocket 324 andthereby enables further travel of the blister strip 302 within thedispenser 300.

FIG. 4 shows a medicament dispenser in accord with the presentinvention, comprising a body 400, a holder 402, refill cassette 404 andelectronic display 406. The holder 402 is shaped to fit snugly insidebody 400 and is fixed to a point on the body (not shown) about which itrotates. Stops 408, 410 protrude from the holder 402 and prevent theholder 402 from rotating more than about 180° relative to the body 400.The stops 408, 410 also provide two defined positions of the holder 402within the body 400. One position is defined by stop 408 meeting withbody edge 412 and the other position defined by stop 410 meeting withbody edge 414 when the holder has been rotated relative to the body. Thearea between stops 408 and 410 is shaped to form a thumb or finger grip416 for the user of the device. The holder 402 forms a shell into whichthe refill cassette 404 snugly fits.

The refill cassette 404 comprises a shell containing the medicamentcarrier (not shown) and a mechanism for opening the carrier (not shown)for the medicament to be accessed. The refill cassette 404 has a raisedportion 418 at one end on both sides along its width so that this partof the refill cassette 404 is at least the same depth as the part of theholder 420 which receives the refill cassette 404. This allows theposition of the cassette 404 within the holder 402 to be fixed such thatthe ridge 418 protrudes from the holder 402 but the rest of the cassette404 is contained within the holder 402.

The refill cassette 404 also has a mouthpiece (not shown) and anindexing lever 422 for indexing the medicament carrier within thecassette 404.

FIGS. 5 a and 5 b illustrate a further refill cassette herein, inperspective and exploded views. The refill cassette housing of FIGS. 5 aand 5 b is shaped for ready receipt by a base unit (not shown) ofsuitable shape/configuration and having general mechanism featuressimilar to those shown in FIG. 1 b.

For clarity, only the principal features of the internal mechanismfeatures of the variations of FIGS. 5 a and 5 b are labelled. The casing500 of the cassette is in combination, formed of base 501 a, top 501 band mouthpiece 501 c casing assembly elements. The casing 500 isgenerally shaped to receive a medicament carrier blister strip (notshown) that coils in chamber 504 and is fed about flexible guidemembrane 506 to the opening station 508 for peeling open thereof.Adjacent to peeling station 508 there is also provided shutter 510 andoutlet stack 511 components, which guide release of medicament to themouthpiece 501 c. After the blister strip is peeled into its separatelid sheet and base sheet components (not shown), the lid sheet feedsonto lid spool 516 and the base sheet onto base spool 518.

There is further provided an index ratchet 520 that includes dogged end522 for reversibly engaging blister strip and actuator lever 521, whichprotrudes from the cassette casing 500. Similarly to the earlierdescribed embodiments of FIGS. 3 a and 3 b, the index ratchet 520 ismovable from a ‘locked position’ in which it doggedly engages theblister strip to prevent its movement to a ‘release position’ in whichit disengages the strip and thereby enables its travel within thedispenser 500 for peeling thereof.

The lid spool 516 and base spool 518 are provided with inner drivespindles 517, 519, each of which has a drive head with plural teeth 577,579 for drivable engagement thereof by base unit drive elements (notshown). It will be appreciated that the respective drive heads have agenerally flat profile, which in use (see FIG. 5 a) protrudes onlyslightly from the casing 500 thereby enabling ready receipt of therefill cassette by the base unit. The lid spool 516 is further providedwith an index spring 576 and the base spool 518 further provided with anon-return ratchet 578 which co-operates with non-return leg 575 mouldedinto the casing body 501 a.

It may be appreciated that any of the parts of the dispenser or cassettewhich contact the medicament suspension may be coated with materialssuch as fluoropolymer materials (e.g. PTFE or FEP) which reduce thetendency of medicament to adhere thereto. Any movable parts may alsohave coatings applied thereto which enhance their desired movementcharacteristics. Frictional coatings may therefore be applied to enhancefrictional contact and lubricants (e.g. silicone oil) used to reducefrictional contact as necessary.

The medicament dispenser of the invention is suitable for dispensingmedicament, particularly for the treatment of respiratory disorders suchas asthma and chronic obstructive pulmonary disease (COPD).

Appropriate medicaments may thus be selected from, for example,analgesics, e.g. codeine, dihydromorphine, ergotamine, fentanyl ormorphine; anginal preparations, e.g., diltiazem; antiallergics, e.g.,cromoglycate (eg as the sodium salt), ketotifen or nedocromil (eg as thesodium salt); antiinfectives e.g., cephalosporins, penicillins,streptomycin, sulphonamides, tetracyclines and pentamidine;antihistamines, e.g., methapyrilene; anti-inflammatories, e.g.,beclomethasone (eg as the dipropionate ester), fluticasone (eg as thepropionate ester), flunisolide, budesonide, rofleponide, mometasone (egas the furoate ester), ciclesonide, triamcinolone (eg as the acetonide),6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxy-androsta-1,4-diene-17β-carbothioicacid S-(2-oxo-tetrahydro-furan-3-yl) ester or6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioicacid S-fluoromethyl ester; antitussives, e.g., noscapine;bronchodilators, e.g., albuterol (eg as free base or sulphate),salmeterol (eg as xinafoate), ephedrine, adrenaline, fenoterol (eg ashydrobromide), formoterol (eg as fumarate), isoprenaline,metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol (eg asacetate), reproterol (eg as hydrochloride), rimiterol, terbutaline (egas sulphate), isoetharine, tulobuterol or4-hydroxy-7-[2-[[2-[[3-(2-phenylethoxy)propyl]sulfonyl]ethyl]amino]ethyl-2(3H)-benzothiazolone;PDE4 inhibitors eg cilomilast or roflumilast; leukotriene antagonists egmontelukast, praniukast and zafirlukast; adenosine 2a agonists, e.g.2R,3R,4S,5R)-2-[6-Amino-2-(1S-hydroxymethyl-2-phenyl-ethylamino)-purin-9-yl]-5-(2-ethyl-2H-tetrazol-5-yl)-tetrahydrofuran-3,4-diol(e.g. as maleate); α₄ integrin inhibitors e.g.(2S)-3-[4-({[4-(aminocarbonyl)-1-piperidinyl]carbonyl}oxy)phenyl]-2-[((2S)-4-methyl-2-{[2-(2-methylphenoxy)acetyl]amino}pentanoyl)amino]propanoic acid (e.g. as free acid or potassium salt), diuretics, e.g.,amiloride; anticholinergics, e.g., ipratropium (eg as bromide),tiotropium, atropine or oxitropium; hormones, e.g., cortisone,hydrocortisone or prednisolone; xanthines, e.g., aminophylline, cholinetheophyllinate, lysine theophyllinate or theophylline; therapeuticproteins and peptides, e.g., insulin or glucagons. It will be clear to aperson skilled in the art that, where appropriate, the medicaments maybe used in the form of salts, (e.g., as alkali metal or amine salts oras acid addition salts) or as esters (e.g., lower alkyl esters) or assolvates (e.g., hydrates) to optimise the activity and/or stability ofthe medicament.

Preferred medicaments are selected from albuterol, salmeterol,fluticasone propionate and beclomethasone dipropionate and salts orsolvates thereof, e.g., the sulphate of albuterol and the xinafoate ofsalmeterol.

Medicaments can also be delivered in combinations. Preferredformulations containing combinations of active ingredients containsalbutamol (e.g., as the free base or the sulphate salt) or salmeterol(e.g., as the xinafoate salt) or formoterol (eg as the fumarate salt) incombination with an anti-inflammatory steroid such as a beclomethasoneester (e.g., the dipropionate) or a fluticasone ester (e.g., thepropionate) or budesonide. A particularly preferred combination is acombination of fluticasone propionate and salmeterol, or a salt thereof(particularly the xinafoate salt). A further combination of particularinterest is budesonide and formoterol (e.g. as the fumarate salt).

Generally, powdered medicament particles suitable for delivery to thebronchial or alveolar region of the lung have an aerodynamic diameter ofless than 10 micrometers, preferably less than 6 micrometers. Othersized particles may be used if delivery to other portions of therespiratory tract is desired, such as the nasal cavity, mouth or throat.The medicament may be delivered as pure drug, but more appropriately, itis preferred that medicaments are delivered together with excipients(carriers) which are suitable for inhalation. Suitable excipientsinclude organic excipients such as polysaccharides (i.e. starch,cellulose and the like), lactose, glucose, mannitol, amino acids, andmaltodextrins, and inorganic excipients such as calcium carbonate orsodium chloride. Lactose is a preferred excipient.

Particles of the powdered medicament and/or excipient may be produced byconventional techniques, for example by micronisation, milling orsieving. Additionally, medicament and/or excipient powders may beengineered with particular densities, size ranges, or characteristics.Particles may comprise active agents, surfactants, wall formingmaterials, or other components considered desirable by those of ordinaryskill.

The excipient may be included with the medicament via well knownmethods, such as by admixing, co-precipitating and the like. Blends ofexcipients and drugs are typically formulated to allow the precisemetering and dispersion of the blend into doses. A standard blend, forexample, contains 13000 micrograms lactose mixed with 50 microgramsdrug, yielding an excipient to drug ratio of 260:1. Dosage blends withexcipient to drug ratios of from 100:1 to 1:1 may be used. At very lowratios of excipient to drug, however, the drug dose reproducibility maybecome more variable.

It will be understood that the present disclosure is for the purpose ofillustration only and the invention extends to modifications, variationsand improvements thereto.

The application of which this description and claims form part may beused as a basis for priority in respect of any subsequent application.The claims of such subsequent application may be directed to any featureor combination of features described therein. They may take the form ofproduct, method or use claims and may include, by way of example andwithout limitation, one or more of the following claims:

1. A medicament dispenser for use with a medicament carrier having aplurality of pockets for containing medicament wherein said pockets arespaced along the length of and defined between two peelable sheetssecured to each other, said dispenser having an internal mechanism foraccessing said medicament contained within said medicament carrier, saidmechanism comprising, a) an opening station for receiving a pocket ofsaid medicament carrier; b) peeling means positioned to engage a basesheet and a lid sheet of a pocket which has been received in saidopening station for peeling apart such a base sheet and lid sheet, toopen such a pocket, said peeling means including lid driving means forpulling apart a lid sheet and a base sheet of a pocket that has beenreceived at said opening station; c) an outlet, positioned to be incommunication with an opened pocket through which a user can removemedicament from such an opened pocket; and d) indexing means forindexing in communication with said outlet, pockets of a medicamentcarrier in use with said medicament dispenser, wherein said indexingmeans comprises an index ratchet which is movable between a lockedposition in which said ratchet engages said medicament carrier toprevent movement thereof and a release position in which the ratchetdisengages from the medicament carrier to allow movement thereof forpeeling open of a blister pocket.
 2. A medicament dispenser according toclaim 1, wherein actuation of said medicament dispenser actuates saidlid driving means and disengages said index ratchet from the medicamentcarrier.
 3. A medicament dispenser according to claim 1, wherein theindex ratchet comprises a ratchet arm.
 4. A medicament dispenseraccording to claim 3, wherein said ratchet arm is pivotally mounted onthe dispenser.
 5. A medicament dispenser according to claim 1, whereinin the locked position the index ratchet engages a blister pocket ofsaid medicament carrier and in the release position said pocket isdisengaged.
 6. A medicament dispenser according to claim 5, wherein theindex ratchet is positioned to cam in and out of engagement with saidblister pocket of the medicament carrier.
 7. A medicament dispenseraccording to claim 1, further comprising an indexing lever for actuatingsaid dispenser.
 8. A medicament dispenser according to claim 7, whereinsaid indexing lever comprises cam means for moving said index ratchetbetween locked and release positions, such that actuation of said leverfrom a stop position releases said medicament carrier for peelingthereof.
 9. A medicament dispenser according to claim 7, wherein saidindexing lever comprises a lever ratchet for engaging said lid drivingmeans.
 10. A medicament dispenser according to claim 1, wherein said liddriving means comprises an index gear and a drive gear which areinterconnected so that the rotation of one correlates with the rotationof the other.
 11. A medicament dispenser according to claim 11, whereinsaid lid driving means comprises a wheel on which the lid sheet is woundup.
 12. A medicament dispenser according to claim 11, wherein said lidsheet wheel has an effective winding surface the diameter of whichincreases after every use of the dispenser.
 13. A medicament dispenseraccording to claim 7, further comprising a lever stop means to limit theextent of movement of said index lever and thereby said lid drivingmeans, in order to control the length of medicament carrier peeled bysaid peeling means.
 14. A medicament dispenser according to claim 13further comprising compensating means positioned between said openingstation and said lid sheet wheel for reducing the length of lid sheettherebetween to compensate for any increase in the diameter of saideffective winding surface of the lid sheet wheel during use of thedispenser.
 15. A medicament dispenser according to claim 14, wherein thecompensating means takes the form of a flexible member.
 16. A medicamentdispenser according to claim 15, wherein the flexible member takes theform of a flexible elongate arm about which the lid sheet is fed.
 17. Amedicament dispenser according to claim 15, wherein the compensatingmeans takes the form of a spring which reduces in length as tension inthe lid sheet increases.
 18. A medicament dispenser according to claim17, wherein a piston head is mounted on one end of the spring, aboutwhich the lid sheet is fed.
 19. A medicament dispenser according toclaim 14, wherein the compensating means takes the form of a springloaded tensioner.
 20. A medicament dispenser according to claim 15,wherein the compensating means are resilient.
 21. A medicament dispenseraccording to claim 12 further comprising clutch means, in communicationwith the indexing means and the lid sheet wheel to accommodate for anyincrease in the diameter of said effective winding surface of the lidsheet wheel during use of the dispenser.
 22. A medicament dispenseraccording to claim 21, wherein said clutch means comprising a gearingsurface defining plural gear engagement positions; and plural gear teethfor engaging said plural gear engagement positions, and the plural gearteeth are arranged such that at any one time only a single gear toothengages a single gear engagement position.
 23. A medicament dispenseraccording to claim 22, wherein the gearing surface and the plural gearteeth are arranged such that the number of individual gear positionsdefinable is equal to the number of gear engagement positions multipliedby the number of gear teeth.
 24. A medicament dispenser according toclaim 22, wherein the gear engagement positions are equally spaced andthe gear teeth are offset relative thereto.
 25. A medicament dispenseraccording to claim 22, wherein the gear engagement positions are equallyspaced and the gear teeth are located on a wobbling element capable ofwobbling the gear teeth to plural offset positions.
 26. A medicamentdispenser according to claim 22, wherein the clutch means isnon-integral with either of the lid driving means or the indexing means.27. A medicament dispenser according to claim 22, wherein the gear teethare arranged in ratchet form.
 28. A medicament dispenser according toclaim 22, wherein the gearing surface and the plural gear teeth arebiased for engagement.
 29. A medicament dispenser according to claim 11,wherein said wheel has a winding surface which decreases in diameterwhen tension in the lid sheet increases.
 30. A medicament dispenseraccording to claim 29, wherein said wheel comprises a plurality ofresiliently flexible arms each extending therefrom at an angle withrespect to a radius.
 31. A medicament dispenser according to claim 1,wherein said lid driving means comprises a mangle.
 32. A medicamentdispenser according to claim 1, wherein said lid driving means comprisesa roller.
 33. A medicament dispenser according to claim 32, wherein saidroller is composed of a polymeric rubber.
 34. A medicament dispenseraccording to claim 1, wherein, said lid driving means comprises (i) aspiked wheel; and/or (ii) a clamp system.
 35. A medicament dispenseraccording to claim 1, wherein the index ratchet and/or the lid drivingmeans are operated by an electronic drive system.
 36. A medicamentdispenser according to claim 35, wherein the electronic drive system isused in conjunction with a mechanical drive system.
 37. A medicamentdispenser according to claim 1, additionally comprising a first chamberto receive the elongated strip of the medicament carrier when the basesheet and lid sheet are peelably sealed together and a second chamber toreceive the base sheet after it has been separated from the lid sheet.38. A medicament dispenser according to claim 37, wherein said firstchamber and said second chamber are separated by a wall.
 39. Amedicament dispenser according to claim 38, wherein said wall is movableto adjust the size of the first and second chambers.
 40. A medicamentdispenser according to claim 39, wherein said wall is flexible to allowchanges to the relative size of the first and second chambers.
 41. Amedicament dispenser according to claim 1, wherein the internalmechanism for accessing the said medicament contained within saidmedicament carrier is housed within a cassette.
 42. A medicamentdispenser according to claim 41 comprising, a body; a holder, shaped tofit within said body and movable relative to said body; and receivableby said holder, said cassette containing said medicament carrier.
 43. Amedicament dispenser according to claim 42, wherein movement of saidholder relative to said body results in movement of said cassettebetween a first position and a second position such that the cassette isreversibly removable from the holder when the cassette is in the secondposition.
 44. A medicament dispenser according to claim 43, wherein thefirst position comprises a dispensing position.
 45. A medicamentdispenser according to claim 44, wherein the second position comprises anon-dispensing position.
 46. A medicament dispenser according to claim42, wherein the holder and body include attaching means to attach theholder to the body.
 47. A medicament dispenser according to claim 46,wherein said attaching means comprise a pin and hole system.
 48. Amedicament dispenser according to claim 42, wherein the holder ispivotally movable relative to the body.
 49. A medicament dispenseraccording to claim 42, wherein the holder is rotationally movablerelative to the body.
 50. A medicament dispenser according to claim 48,wherein the holder additionally comprises a stop to limit movement ofthe holder relative to the body to 180°.
 51. A medicament dispenseraccording to claim 42, wherein the holder is slidably movable relativeto the body.
 52. A medicament dispenser according to claim 42, whereinthe holder additionally comprises a catch to retain the cassette.
 53. Amedicament dispenser according to claim 52, wherein the catch is childresistant.
 54. A medicament dispenser according to claim 48, wherein thecassette additionally comprises an indexing lever.
 55. A medicamentdispenser according to claim 42, wherein the cassette additionallycomprises a mouthpiece.
 56. A medicament dispenser according to claim37, wherein the body covers the mouthpiece and indexing lever when thecassette is in the non-dispensing position.
 57. A medicament dispenseraccording to claim 37, wherein the cassette additionally comprises araised portion to fit against the holder.
 58. A medicament dispenseraccording to claim 37, wherein at least a portion of the body is shapedfor ease of grip by the user.
 59. A medicament dispenser according toclaim 37, wherein operation of the device may be performed with onehand.
 60. A medicament dispenser according to claim 1 additionallycomprising a medicament carrier comprising medicament in powdered orcompacted solid form.
 61. A medicament dispenser according to 60,wherein the medicament comprises a drug.
 62. A medicament dispenseraccording to claim 61, wherein the drug is selected from the groupconsisting of albuterol, salmeterol, fluticasone propionate andbeclomethasone dipropionate and salts or solvates thereof and anycombination thereof.
 63. A medicament dispenser according to claim 62,wherein said combination comprises salmeterol xinafoate and fluticasonepropionate.
 64. A medicament dispenser according to claim 61, whereinthe medicament additionally comprises an excipient.
 65. A medicamentdispenser according to claim 64, wherein the excipient is a sugar.
 66. Akit of parts comprising a cassette according to claim 41, a holder forsaid cassette and a body wherein the holder is shaped to fit within saidbody and is movable relative to said body.
 67. A method of dispensing amedicament comprising, a. providing a medicament dispenser according toclaim 1, and b. dispensing medicament therefrom.